Despite large-scale public health efforts, the problem of adolescent substance use and emerging dependence continues. To enhance prevention efforts, theorists have sought to understand factors that contribute to the etiology and maintenance of adolescent substance misuse. Several converging theoretical perspectives suggest that the reduction or avoidance of aversive internal states (i.e., negative reinforcement) strongly motivates addictive drug use. Indeed, the adult and adolescent literatures support the role of negative reinforcement processes in both substance use initiation and dependence. Despite the widespread acceptance of negative reinforcement models of substance misuse, the field currently lacks adequate behavioral strategies to assess the complex nature of negative reinforcement processes in humans. Moreover, the neural systems that support negative reinforcement processes have not been well studied in humans. Thus, development of adequate behavioral assessment strategies, especially those informed by neuroimaging considerations, can aid in improving our understanding of the range of processes engaged by the human brain to avoid aversive outcomes. Starting with a well-validated behavioral task that addresses the positive reinforcement aspects of substance use (Balloon Analogue Risk Task, BART), the goal of this R21 application is to develop a parallel version of the task focused on negative reinforcement processes (BART-NR). Moreover, this program of research will address the limitation of behavioral measurement when used alone, in that it is restricted typically to the level of description. To address this issue, we propose the development of the new negative reinforcement BART using high density EEG, with this work setting the stage for future work using fMRI methods. We will begin with a pilot test using 10 participants to develop and refine the methods and procedures for a larger study adequately powered with 145 adolescent subjects, aged between 15 and 17 years, to examine neurophysiological (dense array EEG) factors underlying behavior on our negative reinforcement task. Our approach provides an opportunity to move beyond description into understanding the cumulative influence of positive and negative reinforcement processes underlying adolescent substance use and associated risk behavior. In addition to adding to knowledge at a more basic level, this work also may have more long-range applied implications for the development of more effective and targeted interventions for adolescents at risk for substance use;specifically, those for whom substance use or other risky behaviors serve as a means to reduce aversive negative affect. PUBLIC HEALTH RELEVANCE: Current behavioral tasks focus on the appetitive and positive reinforcement aspects of substance use but largely ignore the crucial parallel processes of negative reinforcement. The goal of this application is to develop a comprehensive behavioral and neurophysiological assessment approach for understanding the role of negative reinforcement in adolescent substance use, with a focus on the current use of EEG methods and longer-term development of an fMRI-appropriate version. In addition to adding to knowledge at a more basic level, this work also may have more long-range applied implications for the development of more effective and targeted interventions for adolescents at risk for substance use;specifically, those for whom substance use or other risky behaviors serve as a means to reduce aversive negative affect.